moving from control to elimination of schistosomiasis in sub saharan africa time to change and adapt strategies

Keywords: Schistosomiasis, Control, Elimination, Mapping, Diagnostics, Preventive chemotherapy, Mass drug administration, Sub-Saharan Africa Multilingual abstracts Please see Additional

S C O P I N G R E V I E W Open Access

Moving from control to elimination of

schistosomiasis in sub-Saharan Africa: time

to change and adapt strategies

Louis-Albert Tchuem Tchuenté1,2*, David Rollinson3, J Russell Stothard4and David Molyneux4

Abstract

Schistosomiasis is a water borne parasitic disease of global importance and with ongoing control the disease

endemic landscape is changing In sub-Saharan Africa, for example, the landscape is becoming ever more

heterogeneous as there are several species of Schistosoma that respond in different ways to ongoing preventive chemotherapy and the inter-sectoral interventions currently applied The major focus of preventive chemotherapy is delivery of praziquantel by mass drug administration to those shown to be, or presumed to be, at-risk of infection and disease In some countries, regional progress may be uneven but in certain locations there are very real

prospects to transition from control into interruption of transmission, and ultimately elimination To manage this transition requires reconsideration of some of the currently deployed diagnostic tools used in surveillance and downward realignment of existing prevalence thresholds to trigger mass treatment A key challenge will be

maintaining and if possible, expanding the current donation of praziquantel to currently overlooked groups, then judging when appropriate to move from mass drug administration to selective treatment In so doing, this will ensure the health system is adapted, primed and shown to be cost-effective to respond to these changing disease dynamics as we move forward to 2020 targets and beyond

Keywords: Schistosomiasis, Control, Elimination, Mapping, Diagnostics, Preventive chemotherapy, Mass drug

administration, Sub-Saharan Africa

Multilingual abstracts

Please see Additional file 1 for translations of the

ab-stract into the six official working languages of the

United States

Introduction

Schistosomiasis is a waterborne infection and is one of

the most common parasitic diseases in the world, and is

of public health global importance [1] This disease has

major health and socio-economic repercussions, and

constitutes an important public health problem in

devel-oping countries as well as a significant hazard for

visi-tors and travellers who visit disease endemic regions

Human schistosomiasis is caused by six species of

schistosomes, i.e Schistosoma haematobium, S mansoni,

S japonicum, S mekongi, S intercalatum and S guineen-sis; and is endemic in 78 countries [1, 2] Of these six species, S haematobium is responsible for urogenital schistosomiasis and has significant interactions with HIV and also HPV [3], whilst other species each cause intestinal or rectal schistosomiasis It is estimated that

779 million people are at risk of infection, and about

250 million people are currently infected [2, 4] The Glo-bal Burden of Disease study of 2010 attributed some 3.31 million disability-adjusted life years (DALYs) and 11

700 death per year to schistosomiasis, a mortality figure which has been challenged as a gross underestimate [5] Schistosomiasis affects the poorest of the poor and in-fections are particularly abundant among people living

in rural or deprived urban or peri-urban settings [6] These populations typically have low socio-economic status with limited access to clean water and with inad-equate sanitation provision [7, 8] The morbidity caused

* Correspondence: tchuemtchuente@schisto.com

1

National Programme for the Control of Schistosomiasis and STH, Ministry of

Public Health, Yaoundé, Cameroon

2 Centre for Schistosomiasis and Parasitology, University of Yaoundé I,

Yaoundé, Cameroon

Full list of author information is available at the end of the article

© The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made The Creative Commons Public Domain Dedication waiver

by schistosomes is commonly associated with

moderate-to-heavy egg-infection intensities and is progressive; as

compared with any other age group, school-aged

chil-dren and pre-school chilchil-dren are the most vulnerable

groups to developing overt disease [9, 10] These groups

typically harbour the largest numbers of adult worms,

with copious tissue entrapped eggs causing systematic

and organ-specific inflammation, concomitantly when

the consequences of this infection causes greatest

physiological and developmental insult [2] Studies have

demonstrated that children can acquire schistosome

in-fections within the first few months of life [11, 12],

caus-ing early life initial organ damage and altered

development, mediated by fibrotic lesions around

tissue-trapped eggs, manifesting overtly in adolescence and

early adulthood [9, 13]

Successful schistosomiasis control programmes in

Japan, China, Philippines, Brazil, Egypt and in some

sub-Saharan African countries have shown that control of

schistosomiasis with progression towards elimination of

disease is feasible [14] The recent impetus for

schisto-somiasis control has generated a greater political

com-mitment, as well as an unprecedented opportunity for

cost-effective action [15, 16] This momentum has

en-couraged many countries to establish national action

plans and programmes to control neglected tropical

dis-eases (NTDs) [7, 17, 18]

Within the past decade, significant progress has been

made on large scale treatments through integrated

con-trol of schistosomiasis and other NTDs, thanks to a

number of international organizations, donor

founda-tions, bilateral institutions and non-governmental

orga-nizations that responded to the WHO’s 2001 call for

action [19] Today, treatment with praziquantel [20] is

cost-effective and‘preventive chemotherapy’ is currently

the strategy of choice and endorsed by WHO [9, 21]

With a support from the USAID and the UK

Depart-ment for International DevelopDepart-ment (DFID), as well as

the Bill and Melinda Gates Foundation, the

pharmaceut-ical industry, and several not-for profit organizations,

millions of children are regularly treated for

schistosom-iasis and other NTDs simultaneously, through

coordi-nated use of anthelminthic drugs [22, 23]

In the past, a key bottleneck to implementation of

pre-ventive chemotherapy for control of schistosomiasis in

sub-Saharan Africa was the limited access to

praziquan-tel, either purchased or donated [24] From 2002, with

the expansion of activities of the Schistosomiasis Control

Initiative, it was clear that the future need for large-scale

quantities of praziquantel would grow [18] In 2007,

Merck KGaA pledged to donate 200 million tablets of

praziquantel over 10 years through WHO However, in

2012, Merck-KGaA committed to increase its donation

to 250 million tablets of praziquantel per year until

schistosomiasis is eliminated To bolster this donation, additional amounts of praziquantel and resources for implementation were provided by other partners Whilst there is now growing access to praziquantel for schisto-somiasis control in sub-Saharan Africa, it is not at the level of projected requirements to reach all people at risk and requiring treatment [25] Analysis of data re-ported on treatment coverage for schistosomiasis show that utilization of available praziquantel by NTD pro-grammes is not yet optimal in many countries [22, 23] Furthermore, special attention is needed to develop new access plans and reporting frameworks to vulnerable demo-graphic groups in high-risk areas, particularly pre-school-aged children who are currently overlooked [10, 26] However, the control of schistosomiasis is a long-term undertaking which involves several challenges Current strategies were designed primarily for the control of morbidity due to schistosomiasis and were formulated over two decades ago when the availability of praziquan-tel was limited [27, 28] The new impetus towards schis-tosomiasis elimination requires some modification, adaptation and even change of strategies [14, 29, 30], which concomitantly raises new challenges and points for consideration [31, 32] This paper highlights the pro-gress made and reviews the main challenges and require-ments to move from control to elimination of schistosomiasis in sub-Saharan Africa

Schistosomiasis and the global health agenda

In 1975, the World Health Assembly (WHA) adopted the WHA 28.53 resolution calling for the preparation of guidelines and increased efforts in drug development, water projects and partner mobilization for schistosom-iasis control [27] The following year, in 1976, the WHA29.58 resolution urged endemic countries to con-sider the epidemiological aspects of schistosomiasis when planning and implementing water management schemes, and to undertake specific measures to prevent the spread of the disease into new areas and neighboring countries [33] However, despite the existence of tools in the 1970s and 1980s, control of schistosomiasis was only sustained for a prolonged period in a few coun-tries and almost no progress was made in sub-Saharan African countries, the most endemic part of the world In the 1990s, interest in the control of schistosomiasis in Africa waned, and disease control was overshadowed by other health priorities [34] through an era of health sector reform and World Bank driven Structural Adjustment Programmes Recent years have witnessed an increased interest in the control/elimination of NTDs, and today the control

of schistosomiasis has again become a priority on the agenda of many governments, donors, pharmaceutical companies and international agencies This has been

catalysed by several other WHA resolutions In 2001, all

member states of WHO endorsed the WHA54.19

reso-lution on schistosomiasis and STH, with the major

ob-jective of the regular treatment of at least 75% of all

school-aged children at risk of morbidity by 2010 [28]

This resolution generated a greater political

commit-ment and encouraged many countries to establish

na-tional action plans and programmes for schistosomiasis

and STH control Ten years later, in January 2012,

WHO published an NTD Roadmap that set targets for

the period 2012–2020, and described the strategic

ap-proach to accelerate work to overcome the global impact

of NTDs This roadmap identified preventive

chemo-therapy as a key strategy for tackling NTDs which

responded to mass chemotherapy [21, 35] At the same

time (January 2012), partners and stakeholders

(pharma-ceutical companies, donors, endemic countries,

Non-Governmental Organizations) endorsed the London

dec-laration on NTDs, and committed to support the WHO

roadmap and its 2020 targets for 10 NTDs In response,

the pharmaceutical sector committed to donate all

re-quired drugs for as long as necessary [36]

Still in 2012, WHO member states endorsed the

WHA65.21 resolution on elimination of schistosomiasis,

that called on all endemic countries to intensify control

interventions and strengthen surveillance Importantly,

this resolution urged countries to embark on

schisto-somiasis elimination where possible [35] This change of

policy was a bold and important step towards the

elim-ination of schistosomiasis Finally, in 2013, the

WHA66.12 resolution on NTDs urged countries to

en-sure continued country ownership of programmes for

NTD prevention, control, elimination and eradication;

to further strengthen disease surveillance system; to

ex-pand and implement appropriate interventions against

NTDs; to advocate for funding; to strengthen capacity

for NTD prevention, control, monitoring and evaluation;

to devise plans for achieving and maintaining universal

access to and coverage with interventions against NTDs,

including provision of safe drinking-water, basic

sanita-tion, health promotion and education [1]

Clean water provision, sanitation and hygiene (WASH)

are critical components in the prevention and care for

all NTDs scheduled for intensified control or elimination

by 2020 For schistosomiasis, improved sanitation across

the entire community to prevent contaminated faeces

and urine from reaching surface water can reduce or

eliminate transmission, by stopping worm eggs in faeces

and urine from entering water–the snail habitat

Provision of safe water, sanitation and hygiene is one of

the five key interventions within the global NTD

road-map This requires a strong intersectoral collaboration

WASH providers must prioritize reduction of

inequal-ities to align with the Sustainable Development Goals’

agenda, as developed in the recent WASH strategy to accelerate and sustain progress on NTDs [37]

The WHO NTD roadmap set three time-bound goals for the control or elimination of schistosomiasis First,

2015 for the elimination of schistosomiasis in the East-ern Mediterranean Region, the Caribbean, Indonesia and the Mekong River basin Second, 2020 for schistosomia-sis elimination in the Americas and Western Pacific Re-gions; and potential elimination as a “public health problem” in multiple countries in Africa Although schistosomiasis was not yet scheduled for elimination in sub-Saharan Africa by 2020, the roadmap envisaged po-tential elimination in selected countries or parts of countries where conditions were appropriate, such as Zanzibar (United Republic of Tanzania) where a con-certed effort was on-going (SCORE project and China-Africa initiative) Finally, the roadmap set a potential global elimination of schistosomiasis as a“public health problem” by 2025 [1, 31, 36]

Progress in the control of schistosomiasis in SSA

A key aspect within the WHO Roadmap was making the burden of schistosomiasis much more explicit which then allowed calculation and forecasting of future prazi-quantel requirements for each country There has been substantial progress towards WHO Roadmap goals for schistosomiasis and regional targets, as the control of schistosomiasis has become a priority on the agenda of many governments This momentum has encouraged many countries to establish national action plans and programmes to control NTDs [7, 17, 38] By 2016, 36 African countries had developed and launched their na-tional NTD master plans With a support from USAID and UK Department of International Development (DFID) governments, as well as the Bill and Melinda Gates Foundation, the pharmaceutical industry, and many not-for profit organizations, the mapping of NTDs has been completed and millions of children are regu-larly treated for schistosomiasis and other NTDs

Mapping the schistosomiasis distribution

Although the African region bears a disproportionately high burden of schistosomiasis, the mapping of disease prevalence remained incomplete in many countries In January 2014, the WHO Regional Office for Africa (AFRO) launched a mapping initiative targeting to the completion of the mapping of the five NTDs amenable to preventive chemotherapy (lymphatic filariasis, onchocer-ciasis, schistosomiasis, STH and trachoma) in all countries

of the African region Funded by the Bill and Melinda Gates Foundation, this project enabled the acceleration of the completion of Preventive Chemotherapy amenable NTD mapping in the WHO African region

Through a coordinated NTD mapping framework,

strong WHO AFRO support, the deployment of a

pool of well-trained NTD expert and mapping

spe-cialists, and a strong commitment by governments,

significant progress has been made in the mapping of

PC NTDs in the African region within the past 3

years By June 2016, mapping of PC NTDs, including

schistosomiasis, was completed in 41 countries of the

47 countries of the WHO African region, and there

remained only six countries where mapping was still

ongoing: Algeria, Angola, Central Africa Republic,

Ethiopia, South Africa, and South Sudan [39] This

achievement was a critical step to enable the

com-mencement of interventions towards the 2020/2025

schistosomiasis control and elimination targets

Treatment

Considerable progress is being made in scaling-up

pre-ventive chemotherapy interventions in sub-Saharan

Af-rica With a support from USAID, DFID, BMGF, the

pharmaceutical industry and many not for profit

organi-zations, millions of children are regularly treated for

schistosomiasis and other NTDs Within the past 10

years, the number of people treated for schistosomiasis

in the WHO African region has significantly increased

from about 7 million in 2006 to more than 52 million in

2014, corresponding to a scaling up of coverage from

5.47% in 2006 to 20.13% in 2014 [23]

In the more recent report on schistosomiasis

treat-ment worldwide, WHO estimated that the total number

of people requiring treatment for schistosomiasis in

2015 was 218 700 000 (vs 258 875 452 in 2014), of

whom 92.04% lived in the African Region Reports on

the annual progress on preventive chemotherapy

inter-ventions received in WHO by 20 September 2016

re-vealed that 27 African countries (vs 23 in 2014) had

reported their treatment data for 2015 by then From this interim report, the number of people treated in the Region was 57 400 000 in 2015 compared to 52 413 796

in 2014 and 26 489 501 in 2013 The number of school-age children that received treatment for schistosomiasis

in 2015 was 46 600 000 (vs 43 725 454 in 2014), repre-senting 81.2% of the total number of people treated in the African region [22, 23, 40] Figure 1 illustrates the steady progress in schistosomiasis treatment in Africa since 2006 The increase of the number of treatments could be explained by several factors: the increased sup-ply of praziquantel essentially from the Merck KGaA do-nation, new countries starting to implement preventive chemotherapy for schistosomiasis, geographical scale up

of the treatment within countries and an improvement

in the reporting

The summary of the global update of preventive chemotherapy implementation in 2015 revealed a signifi-cant improvement in the treatment coverage, reaching for schistosomiasis up to 41.8 and 40.8% for school-aged children at the global and African regional levels, re-spectively However, we are still very far from the target, and there is a need to strengthen programme perfor-mances to scale-up the preventive implementation and increase the coverage

Challenges and requirements

Moving from control to elimination of schistosomiasis is

a paradigm shift that creates several challenges Current interventions and strategies were designed for morbidity control or the elimination of schistosomiasis as a“public health problem” [9, 29] The interruption of schistosom-iasis transmission is a long-term undertaking but re-quires significant changes in the approach, design and strategies with a focus on reducing transmission and preventing reinfection This involves several challenges

Fig 1 Evolution of the number of people treated for schistosomiasis and treatment coverage in the WHO African region, between 2006

and 2015

such as implementation of intensified interventions,

ex-pansion of treatment coverage, use of alternative

strat-egies, improvement of clean water supply, sanitation and

hygiene, health education, funding for interventions,

monitoring and evaluation, and strengthening of

institu-tional capacities and surveillance response system The

present analysis highlights some of the key challenges

and requirements for schistosomiasis elimination in

sub-Saharan Africa

Moving from MDA focused intervention to

complementary public-health interventions

The ultimate goal of all schistosomiasis intervention efforts

should be the elimination of this infection Several

pro-grammatic steps are recognized for the control and

elimin-ation of schistosomiasis [14] These steps require specific

interventions, including interventions for morbidity control

and those for infection prevention It is recommended that

schistosomiasis endemic countries progressively scale-up

their objective from control of morbidity to elimination as

a public health problem, and finally interruption of

trans-mission While moving through these steps, activities

should be reorganized gradually Currently, morbidity

con-trol is the objective in many countries and interventions are

limited to chemotherapy with praziquantel [23, 41]

How-ever, it is known that treatment alone will not be sufficient

to achieve the interruption of schistosomiasis transmission

[42] Therefore, if the elimination goals for schistosomiasis

are to be met, endemic countries should adopt a final push

approach combining intensified preventive chemotherapy

and the implementation of complementary public-health,

environmental and educational interventions Such

intensi-fied preventive chemotherapy consists of implementing the

distribution of praziquantel more frequently, and/or to

ex-tend the treatment to population groups that are different

than those targeted so far [31, 32]

Complementary public-health interventions include

health education for behaviour change, provision of safe

water and sanitation, environmental management and

snail control This combined approach is recommended

in areas approaching elimination as a public-health

problem, and is essential when interruption of

transmis-sion is at the objective In the Regional Strategic Plan for

schistosomiasis, WHO/AFRO defined this approach as

PHASE, standing for preventive chemotherapy, health

education, access to clean water, sanitation

improve-ment, and environmental snail control and focal

mollus-ciciding [14] Increasing access to safe water is an

intervention that will significantly reduce the risk of

schistosomiasis transmission Its achievement requires

inter-sectoral collaboration and partnership However,

most countries cannot raise the resources required to

drastically increase safe water supply Thus, in most

schistosomiasis endemic countries, natural water bodies

(many of which are infested with snails and infective schistosome cercariae, sometimes of zoonotic origin) continue to be the only sources of domestic water and high risk communities cannot avoid reinfections even if they were effectively treated A further challenge is to address the needs of those where occupational exposure

is a daily feature of tending, for example, to agricultural work and fishery [43]

Poor sanitation is a major contributor to transmission

of schistosomiasis and causes rapid re-infection among treated children and adults Improvement in waste dis-posal and a reduction in open defaecation is essential for achieving interruption of transmission Improvement in sanitation not only contributes to prevention of trans-mission, but also to the prevention of many diarrhoeal diseases Sensitization and mobilization of people to build and use latrines should be strengthened There are two main strategies within WASH that feature participa-tory hygiene and sanitation transformation (PHAST) and community-led total sanitation (CLTS), however, neither of these approaches will effectively reduce the contamination of water sources by schistosome eggs in the urine Environmental management for snail control has not been generally undertaken in the sub-Saharan African region due to cost limitations and lack of identi-fication of the water bodies where this is feasible As snail control is generally challenging especially in large water bodies, there is need to identify areas with high water contact and intensive schistosomiasis transmission

so that targeted snail control can be limited to such loca-tions However, technical capacity and funding to imple-ment reliable snail surveys is lacking in many countries In China, new and effective snail control approaches, envir-onmental modification (i.e alteration of the ecological en-vironments of the snails’ habitats to make their survival difficult) have been developed and adapted to the local situation in snail-infested areas The current China-Africa cooperation for schistosomiasis elimination provides a platform to learn from Chinese experiences, in the control

of intermediate snail hosts [44]

Scaling up treatment

Although significant progress has been made over the recent years to regularly implement MDA in several countries, the global achievement is still distant from the WHO’s target of regular deworming of at least 75% of school-age children at risk Indeed, it is estimated that the global coverage of schistosomiasis treatment in 2015 was only 28% [40] In many countries, school-based deworming interventions still cover only a minority of children considered to be at risk despite the low cost of preventive chemotherapy and their significant impact on health Despite the increase in drug donation, the major constraint to controlling schistosomiasis continues to be

the limited access to praziquantel In 2015, only nine

coun-tries have reached the target threshold treatment of at least

75% of school-age children in the African Region [40]

To reach the schistosomiasis elimination target, there

is an urgent need to accelerate the extent of treatment

to reach all individuals at risk This extension of

prevent-ive treatment for schistosomiasis remains a serious

chal-lenge, and should be conducted at several levels First,

there is a need to accelerate the scaling up of mass drug

administration to reach 100% geographical coverage and

at least 75% of school-aged children in all endemic

countries in the African region This include a challenge

to tackle the big countries such as Nigeria, Democratic

Republic of Congo, Ethiopia and Tanzania which

ac-count for 60% of at risk population not yet entirely

cov-ered by preventive chemotherapy Secondly, there is a

need to extend treatment to the maximum number of

out-of-school school-aged children Children aged 5–14

years, who are the main target group of preventive

chemotherapy, are relatively easily reached through

school based deworming However, most of

out-of-school children are not reached through this platform

Special efforts should be made to extend treatment to

this group Thirdly, there is a need to extend preventive

chemotherapy to adult populations The available

do-nated drugs are for school-aged children primarily, and

therefore adults, especially high risk populations such as

fishermen, irrigation workers, and women are not

treated during deworming campaigns

The risk factor of urogenital schistosomiasis for

infec-tion by HIV in women has been clearly demonstrated

[45, 46], and adolescent girls and women therefore

re-quire treatment with praziquantel in areas endemic for

S haematobium more frequently than in non-endemic

areas, to reduce the risk of development of genital

le-sions Finally, it becomes urgent to recognize the

im-portance of pre-school age children and their need for

treatment Although children aged less than 5 years can

be already infected through passive water contacts

some-times at alarming levels [47, 48], they are currently not

targeted by national chemotherapy campaigns because

of a lack of suitable paediatric formulations of

prazi-quantel [10, 26]

It is important to highlight that if the elimination goal

is to be achieved for schistosomiasis, it will be essential

to extend the preventive chemotherapy to all

popula-tions who need treatment, inclusive of pre-school aged

children, school-aged children, as well as adults

Schisto-somiasis does not just affect school-age children only,

even though they may have the highest prevalence of

in-fection, and possibly the heaviest disease burden

With-out treatment of all those at risk or contributing to

transmission it is not surprising that treatment limited

to children has limited impact in this regard Treating all

the community will increase the impact of preventive chemotherapy, and will allow the reduction of schisto-some reservoirs in the communities and accelerate the interruption of parasite transmission

Reaching hard to reach and vulnerable communities

Today, the coverage of the public-health interventions recommended by the World Health Organization against NTDs may be interpreted as a proxy for univer-sal health coverage and shared prosperity For schisto-somiasis, universal health coverage means that all people

in need should benefit from the preventive chemother-apy and other control/elimination interventions The Sustainable Development Goals (SDGs) are reinforced

by the commitment of global leaders to ensure that “no one is left behind” from development progress over the next 15 years However, equity is not currently achieved for NTDs; hundreds million of the world’s most vulner-able, most disadvantaged people are still left behind, es-pecially the poorest of the poor, who live in the remotest, hardest to reach parts of the countries or the world

Hard to reach and vulnerable communities include communities that are poorly served by local health ser-vices, roads and transport facilities, itinerant fishing and nomadic communities, seasonal migrants, peri-urban settlers and those unwilling to accept health interven-tions (systematic non compliers) A good example are the challenges of reaching fishing communities along the large lakes such as Lake Albert, Lake Victoria and Lake Malawi that border several countries in Eastern Africa, including Uganda, Kenya, Tanzania and Malawi [49–51] There are also areas inadequately covered with prevent-ive chemotherapy due to civil unrest and conflict as well

as health system crisis caused by recent Ebola outbreak

in West Africa [52, 53]

Adapting treatment to transmission dynamics: the need for alternative strategies

Schistosomes have a complex life cycle that requires a freshwater snail intermediate host and a vertebrate de-finitive host in which the parasites can undergo develop-ment This ties transmission to landscapes where people and snails come together at the same water habitat The success of the transmission depends on numerous fac-tors, including biotic and abiotic features, such as cli-matic, physical and chemical factors that affect the survival and development of schistosome parasites and snail host populations [54] as well as socioeconomic and behavioural characteristics of the human community such as water contact behaviour and the adequacy of water and sanitation, which affect the frequency and in-tensity of exposure to infected water [55, 56] The dis-ease transmission is highly focal, and the endemicity

varies significantly from one locality to another, and

from one country to another It is well known that the

patterns and dynamics of transmission of schistosomiasis

present tremendous complexity and variability between

different foci and even within the same foci The most

significant determinants being water contact patterns,

sanitation and hygiene levels, and the abundance and

susceptibility of freshwater snail hosts

The existence of schistosome hotspots–i.e transmission

areas where prevalence and intensities remain high despite

repeated rounds of mass drug administration–has been

demonstrated in several countries [57, 58] For example, a

number of villages near Lake Albert have shown to

main-tain very high levels of infection with S mansoni following

several years of chemotherapy with praziquantel [59]

Similar observations of hotspots infections despite

re-peated treatments have been reported in several other

countries such as Tanzania/Zanzibar, Mali, Kenya, and

Cameroon In Cameroon, we observed hotspots of

trans-mission in several localities around lakes and dams such

as Barombi Kotto in the South West region and

Malan-touen in the West region, where water contacts are highly

intense and lead to high reinfection patterns In these foci

the prevalence rapidly returns near to the initial level

within 6–12 months post-treatment (Fig 2)

To be efficient, preventive chemotherapy should be

re-peated more frequently in such hotspots, at least twice

per year However, the current recommended treatment strategy does not consider the diversity of transmission dynamics, reinfection patterns and the special features

of schistosomiasis transmission foci With the shift to-wards schistosomiasis elimination, there is a need to adapt treatment strategies to the different types of trans-mission settings Urban schistosomiasis may also require more intense and frequent interventions

Mapping quality and uncertainties

The mapping of NTDs is a critical step in understanding where at-risk populations live in order to target effect-ively available resources and to achieve maximum im-pact on disease burden [60] Without reliable mapping information, countries are not able to plan interventions Accurate mapping of disease distribution is therefore a prerequisite for effective implementation of interven-tions to reduce the burden of schistosomiasis [57, 58, 61] Within the past 10 years, significant progress has been made in the mapping of schistosomiasis in the Af-rican region, and mapping was completed in about 40 countries This exercise was supported by various orga-nizations, funders, partners, and research institutions in different countries

In the mapping design for schistosomiasis, the health dis-trict is the implementation unit, and a subsample of up to

Fig 2 Intense water contact leading to high transmission dynamics of schistosomiasis in Barombi Kotto Barombi Kotto, a village located in the

South-West region of Cameroon, is divided in two parts; a mainland and an island This photograph shows a view of the island from the shore of the mainland, and illustrates the intense water exposure of populations There is no school in the island All children leaving in the island go to school in the mainland Therefore, they have contact with water at least twice per day, as they must cross the lake out and in This frequent water exposure leads to rapid and high reinfections with schistosomiasis, that occur even from the same day of treatment in schools Furthermore, there is no water supply in the island; the whole population relies on water from the lake, and 100% of people are at high risk of infections The transmission dynamics and reinfection patterns are significantly different between populations from the island and those living on the mainland Particular attention should be paid to such hotspots that require more regular and intensified interventions

five schools are generally selected for the surveys Due to

the high focality of schistosomiasis transmission,

sub-districts may be considered in certain circumstances

How-ever, financial resources being a major constraint, not every

sub-district in a district can be mapped independently The

mapping design may combine several sub districts into

mapping units, where transmission is likely to be similar,

according to ecological factors affecting schistosomiasis

transmission This may lead to some uncertainties if the site

selection and sample size are not properly undertaken

In-deed, selection of schools should be purposive and should

be guided by previous knowledge in the areas where

trans-mission is known, suspected or more likely to occur, such

as proximity to lakes, streams, and water bodies Schools

should not be selected in the same locality, but selection

should consider geographical distribution of schools in

order to be representative within the health district

Import-antly, due to the high focality of schistosomiasis

transmis-sion, random selection of schools should be avoided

However, different approaches were used in some countries

where national surveys were conducted using random

se-lection of schools in health districts, or using remote

sens-ing technologies to predict schistosomiasis distribution

Studies have demonstrated that using predictive mapping

alone does not provide reliable information for mass drug

administration planning, resulting in overtreatment in some

areas and most importantly under-treatment in areas that

needed it most [62] This raises concerns about the

accur-acy of various mapping data resulting from less robust

techniques that have been used in several countries

Because of the highly focal distribution of the disease,

there is a need for more accurate mapping to deepen the

understanding of the distribution of schistosomiasis and

snails in the country, which should guide programme

deci-sion making for mass drug administration Furthermore,

the maps should be dynamic entities that change with time

as control progresses, necessitating refinement of tools for

updating the original disease maps As elimination moves

forward there will likely be a need to map more geographic

points, with an optimum to get to all schools within health

unit Currently mapping level ratio of surveyed to

non-surveyed schools if about 1:10, but recent work in Namibia

using rapid diagnostic tests have decreased to 1:4, so there

is quite a bit more surveillance could be needed when we

are looking for the possibility of any evidence of having

schistosomiasis [57] Ideally, a knowledge of water contact

sites and an understanding of local transmission should

guide mapping decisions and interventions [63]

Redefining disease endemicity and focality for eligibility

for MDA

The eligibility of health districts for MDA

implementa-tion is determined by the disease endemicity levels

which are generally estimated by the disease prevalence

[9] For each implementation or mapping unit, one prevalence will be estimated and the entire district will

be classified as non-endemic, low, moderate or high-risk area The treatment strategy will be decided based on this classification For schistosomiasis, the initial map-ping is done by collecting stool and/or urine samples in about five schools per district [64] The disease lence of the districts is calculated as the mean preva-lence of all samples from each district This district will then be classified according to the level of this mean prevalence Currently, schistosomiasis endemicity maps are produced on this basis, as well as the subsequent de-cision to implement preventive chemotherapy or not Although this WHO recommended method to esti-mate district endemicity may have been suitable in the past, within the context of morbidity control and paucity

of drug availability and funding, it may not be suitable now elimination is the goal Indeed, due to the high focality of schistosomiasis transmission, there may exist significant difference in infection prevalence between schools within the same districts With such a mixture

of low and high prevalence, considering only the mean prevalence may lead to an underestimation of the dis-ease occurrence within some districts, resulting to their exclusion for treatment For example, a district with one school having 49% prevalence and four schools exhibit-ing 0% prevalence each, will have a mean prevalence of 9.8% As this mean prevalence is below 10%, this district will be classified on the map as not eligible for mass drug administration The consequence would be that in parts of this districts populations will suffer for schis-tosomiasis and its morbidity without intervention from the national authorities It is therefore necessary for national programmes to have the detailed distribu-tion of the disease at the various sub-districts and schools’ levels to guide treatment decisions and avoid misclassifications [57, 63]

To assess the impact of the current determination of endemicity level on treatment decisions, we conducted a detailed analysis of the recent mapping data in Cameroon, comparing the estimation of district endem-icity levels using the mean prevalence in one hand, and the maximum school prevalence for schistosomiasis per health district on the other The results showed that over the total 189 districts mapped, 47 (24.9%) changed their endemicity classification when considering either the mean school prevalence or the higher school preva-lence Detailed analysis of these 47 districts revealed that when considering the mean prevalence, 44.7% of the dis-tricts (n = 21) had an overall prevalence of <10%, and should therefore be entirely excluded for mass drug ad-ministration, despite the fact that in some localities within these districts there exist high transmission foci, with a school prevalence up to 52.8%

For the remaining 26 districts of the 57, they ranged

all within the moderate-risk community group when

using the mean prevalence estimates However, when

using the higher school prevalence, almost all districts

except one (96.2%) changed category, moving from

moderate-risk to high-risk communities

These results, illustrated in Figs 3 and 4, suggested

that the current method of estimation of district

endem-icity significantly underestimates the disease

transmis-sion levels, and therefore reduced the treatment

interventions This underestimation and its impact on

the programme policy decision showed that the way of

determining district endemicity and eligibility to MDA is

not suitable in a context of schistosomiasis elimination

goal, calling for a reassessment of the current policy

The need to change (the current) treatment thresholds

Because morbidity is typically associated with increasing

worm burden (and entrapment of eggs) rather than the

absence or presence of infection, prevalence is

com-monly combined with worm burden (intensity of

infec-tion) to assess the epidemiological situation for

schistosomiasis Worm burden is commonly measured

by the number of eggs per gram (EPG) of faeces or eggs per 10 ml of urine [13] Prevalence and intensity of in-fections are used to classify communities into transmis-sion categories, which enables the appropriate approach

to mass treatment in a community [9] Existing recom-mendations on frequency of treatment and target popu-lations (Table 1) were developed with the aim of controlling morbidity associated with schistosomiasis With the paradigm shift from control to elimination of schistosomiasis, the current recommended treatment strategy and treatment threshold for interventions is not compatible with the permanent interruption of transmis-sion Furthermore, schistosomiasis is a dynamic disease and prevalence within communities can change rapidly from year to year Thus contamination of a water body

by a few remaining infected individuals can give rise to outbreaks of disease that need to be quickly contained

In recent years, the costs of PZQ and the lack of re-sources were major constraints for the elimination of schistosomiasis Today, there is a greater impetus, with increasing funding opportunities and donated PZQ by pharmaceutical companies Time is right to move to-wards schistosomiasis elimination, and for this challenge

Fig 3 Comparison of district endemicity level/classification using either the mean prevalence of schistosomiasis per district (a) or the higher school prevalence within the district (b) in Cameroon

there is a need to adapt the current threshold for

inter-vention (i.e prevalence > 10%) and to define carefully the

implementation unit for PZQ mass drug administration

Treatment algorithms should be re-defined based on

current knowledge and experiences WHO has

recom-mended that after achieving morbidity control,

prevent-ive chemotherapy should be appropriately adjusted to

the new epidemiological conditions by lowering the

prevalence risk thresholds Further, beyond the stage at

which elimination as a public-health problem is

achieved, a more aggressive strategy will be required in

order to attain the more ambitious goal of interrupting

transmission [1] To achieve this goal as set in the WHO

Schistosomiasis Strategic Plan 2012–2020, the preva-lence of heavy-intensity infections should be reduced to less than 5% in all schistosomiasis-endemic countries by

2020, and to less than 1% by 2025 [65]

The need for better diagnostic tools

Because of its simplicity and relatively low-cost, the Kato–Katz technique is widely used for epidemiological field surveys and is recommended by the WHO for sur-veillance and monitoring of schistosomiasis control pro-grammes [66] Though the specificity is high, the sensitivity of Kato–Katz in single stool sample examin-ation is limited by day-to-day variexamin-ation in egg excretion rates, thus leading to measurement error in estimating the presence of infection This is particularly accentu-ated in areas with high proportions of light intensity in-fections [67, 68] In the current era of preventive chemotherapy, the intensification of large-scale interven-tions and repeated mass deworming will significantly re-duce the prevalence and intensities of schistosome infections [69] As a consequence of the increase of low-intensity infections, less intense infections will be often missed if single stool samples are examined by Kato– Katz method, resulting in significant underestimation of prevalence [67] Therefore, there is a need to develop and validate more sensitive diagnostic tools for accurate surveillance and monitoring of schistosomiasis control programmes, and for monitoring of drug efficacy Some studies recommended multiple stool samples in order to avoid underestimating the ‘true’ prevalence and trans-mission potential of the parasite Indeed, it was demon-strated that Kato–Katz examination of three instead of one stool specimen increased the sensitivity of helminth diagnosis, most notably for hookworm and schistosomes [70] However, this has significant cost implications and

Table 1 Recommended treatment strategy for schistosomiasis in preventive chemotherapy (WHO, 2006)

Category Prevalence among

school-aged children

Action to be taken High-risk

community

≥50% by parasitological

methods (intestinal and

urinary schistosomiasis)

Or

≤30% by questionnaire for

visible haematuria (urinary

schistosomiasis)

Treat all school-age children (enrolled and not enrolled) once a year

Also treat adults considered to be at risk (from special groups to entire communities living in endemic areas; see Annex 6 for details on special groups)

Moderate-risk

community

≥10% but <50% by

parasitological methods

(intestinal and urinary

schistosomiasis)

Or

<30% by questionnaire for

visible haematuria (urinary

schistosomiasis)

Treat all school-age children (enrolled and not enrolled) once every 2 years

Also treat adults considered to be at risk (special risk groups only; see Annex 6 for details on special groups)

Low-risk

community

<10% by parasitological

methods (intestinal and

urinary schistosomiasis)

Treat all school-age children (enrolled and not enrolled) twice during their primary schooling age (e.g once on entry and once on exit)

Praziquantel should be available in dispensaries and clinics for treatment of suspected cases

Fig 4 The changing of health district endemicity category for

schistosomiasis in Cameroon, from lower-risk (rose bars) to

moderate-risk (red bars) and high-risk (dark red bars), when moving

from using the current recommended mean district prevalence

(Mean) to using the maximum school prevalence within the district

(Max) The number of districts per category are reported in the

corresponding bars